Is BUB3 p.Gln192Arg (c.575A>G) pathogenic?

BUB3 p.Gln192Arg (c.575A>G) is classified Uncertain significance in BUB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-15). AlphaMissense: ambiguous (0.4948); Very rare (popmax 8.53e-05%, nfe).

How common is BUB3 p.Gln192Arg (c.575A>G) in the general population?

BUB3 p.Gln192Arg (c.575A>G) is very rare (popmax 8.53e-05%, nfe) (gnomAD).

What do computational predictors say about BUB3 p.Gln192Arg (c.575A>G)?

AlphaMissense predicts ambiguous (score 0.4948) — an in-silico prediction, not a clinical call.

BUB3 p.Gln192Arg

c.575A>G · VCV3483274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4948 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.53e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4948	ambiguous
REVEL	0.409	indeterminate
SaProt	LLR -10.24	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.4, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 6,079 bp · p 8.5e-11 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.53e-05% European (non-Finnish) · 1/1,172,702 alleles

Overall 0.000188% 3/1,593,726 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00314%	31,821
European (non-Finnish)grpmax	8.53e-05%	1,172,701

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BUB3
Protein: p.Gln192Arg
Coding: c.575A>G
MANE Select: NM_004725
Type: single nucleotide variant
Location: chr10:123160564 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.10

Full BUB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BUB3 p.Arg314= Likely benign ★★ same type
BUB3 p.Ser197= Likely benign ★★ same type
BUB3 p.Ser198= Likely benign ★★ same type
BUB3 p.Ala131Val Uncertain significance ★ ⚠ same type
BUB3 p.Ala155Val Uncertain significance ★ ⚠ same type
BUB3 p.Ala187Gly Uncertain significance ★ ⚠ same type
BUB3 p.Ala239Gly Uncertain significance ★ ⚠ same type
BUB3 p.Ala292Val Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/bub3-p-gln192arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown